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COLUMBIA  UM>"--^ 

DEPARTMENT  OF  hflii 

College  of  Physicians  and 

437  WEST  FIFTY -NINTH  Si 
NEW  YORK 

€jje  aniber^itp  of  Chicago 

FOUNDED  BY  JOHN  D.  ROCKEFELLER 


RETROGRADE  DEGENERATION  IN  THE 
SPINAL  NERVES 


A  DISSERTATION 

SUBMITTED  TO  THE  FACULTY  OF  THE 

OGDEN  GRADUATE  SCHOOL  OF  SCIENCE 

IN  CANDIDACY  FOR  THE 
DEGREE  OF 

DOCTOR  OF  PHILOSOPHY 


(department  of  neurology) 


BY 

S.  WALTER  RANSON 


Chicago 

December 

i9°5 


€f)c  aniber^itp  of  Chicago 

FOUNDED   BY   JOHN   D.   ROCKEFELLER 


RETROGRADE   DEGENERATION  IN   THE 
SPINAL   NERVES 


A  DISSERTATION 

SUBMITTED  TO  THE  FACULTY  OF  THE 

OGDEN   GRADUATE  SCHOOL  OF  SCIENCE 

IN   CANDIDACY  FOR  THE 
DEGREE  OF 

DOCTOR  OF  PHILOSOPHY 

(department  of  neurology) 


BY 

S.  WALTER  RANSON 


Chicago 

December 

i9°5 


QP3S/ 


Reprinted  from  The  Journal  of  Comparative  Neurology  and  Psychology,  Vol.  XVI,  No.  4,  1906. 


RETROGRADE  DEGENERATION  IN  THE  SPINAL 

NERVES. 


S.  WALTER  RANSON. 


(From  the  Neurological  Laboratory  of  the  University  of  Chicago  and  the  Anatomical    Laboratory    of 

the  St.  Louis  University^)1 

I.  Summary  of  the  Literature. 

Retrograde  degeneration,  sometimes  also  spoken  of  as  "ascend- 
ing degeneration" (Fleming  '97)  and  "indirect  Wallerian  degenera- 
tion" (van  Gehuchten  '03),  is  a  process  resulting  in  the  de- 
struction of  that  portion  of  a  divided  fiber  which  is  still  connected 
with  its  cell  of  origin.  Such  cellulipetal  changes  are  not  in  accord 
with  the  law  of  Waller,  which  requires  that  of  a  divided  nerve 
fiber  only  the  portion  severed  from  its  trophic  center  should  dis- 
integrate, while  all  the  rest  of  the  neurone  remains  intact;  never- 
theless, this  retrograde  degeneration  has  been  observed  by  a  large 
number  of  investigators;  it  has  been  found  in  the  cerebral  as  well 
as  in  the  spinal  nerves  and  occurs  under  certain  conditions  in 
various  fiber  tracts  of  the  central  system. 

The  investigations,  which  lead  to  the  discovery  of  this  form  of 
degeneration,  were  carried  out  in  the  first  instance  upon  the  nerves 
in  the  central  stumps  of  amputated  limbs  and  upon  the  associated 
segments  of  the  spinal  cord.  Experimental  amputation  and  nerve 
resection  in  animals  have  served  to  confirm  the  observations  made 
on  human  material  and  to  eliminate  complications  introduced  by 
the  cause  of  the  amputation  or  by  the  terminal  disease.  Since 
the  cellulipetal  changes  resulting  from  the  section  of  the  spinal 
nerves  are  typical  of  retrograde  degeneration,  it  has  not  seemed 
desirable  to  complicate  matters  by  a  review  of  the  literature  on 
similar  changes  in  the  cerebral  nerves,  nor  in  the  fiber  tracts  of  the 
central  system.     The  observations  along  these  lines  have  been 

JWhile   at  the  St.  Louis    University   the  writer  received  very  valuable  assistance,   both   in  the 
operations  and  the  enumerations,  from  Dr.  Fred.  B.  Whittiker,  to  whom  he  is  especially  indebted. 


4  Journal  of  Comparative  Neurology  and  Psychology. 

very  well  analyzed  by  van  Gehuchten  ('03)  and  briefly  sum- 
marized by  the  present  "writer  ('04).  It  is  also  belieyed  that  we 
may  omit  without  loss  any  mention  of  the  theories  of  the  different 
investigators  concerning  the  nature  and  cause  of  the  cellulipetal 
alterations  resulting  from  the  section  of  nerves. 

In  studying  the  literature  on  retrograde  degeneration  in  the 
spinal  nerves,  it  was  found  convenient  to  arrange  the  results  of  the 
different  investigators  in  tabular  form,  placing  the  changes  found 
in  the  various  parts  of  the  nervous  system  in  separate  columns 
under  the  following  headings:  central  stumps  of  the  severed 
nerves,  ventral  roots,  dorsal  roots,  spinal  ganglia,  the  spinal  cord 
in  general,  the  ventral  horns  and  motor  cells,  the  dorsal  horns  and 
the  dorsal  funiculi.  In  this  way  were  tabulated  the  changes  found 
in  sixty-nine  autopsies  upon  cases  of  more  or  less  long  standing 
amputation.  In  a  separate  table  of  the  same  kind  were  summar- 
ized the  changes  observed  by  eighteen  different  investigators  who 
had  carried  out  experimental  amputation  and  nerve  resection  in 
animals.  When  these  tables  were  completed,  it  was  possible  to 
compare  the  results  of  the  different  investigators  and  see  what 
changes  were  constant  in  any  part  of  the  nervous  system.  It  is 
with  reference  to  these  tables  that  the  following  has  been  written, 
and  for  this  reason  it  has  been  possible  to  make  accurate,  but  at 
the  same  time  very  general,  statements. 

The  first  observation  of  an  alteration  propagated  centrally  along 
the  course  of  an  injured  nerve  was  made  in  1829  Dv  Berard,  who 
noticed  that  the  ventral  roots,  associated  with  the  nerves  of  an  am- 
putated limb,  were  smaller  than  their  fellows  on  the  opposite  side. 
But  it  was  not  until  1868-69  triat  Vulpian  and  Dickinson  aroused 
general  interest  in  the  subject,  an  interest  which  has  led  to  an 
almost  uninterrupted  series  of  investigations  and  even  at  the  pres- 
ent time  has  not  abated.  The  results  of  this  series  of  investiga- 
tions may  be  .stared  rather  briefly. 

In  a  considerable  proportion  of  the  cases,  no  notice  was  taken  of 
the  central  stumps  of  the  severed  nerves.  Of  those  who  did  in- 
clude these  structures  in  their  investigations  only  two  found  them 
normal  (Friedreich '73,  and  Dreschfeld  '79).  The  complete 
degeneration,  seen  in  one  of  Dickinson's  ('68)  cases,  was  undoubt- 
edly due  to  extraneous  causes,  probably  septic  infection.  In  all  the 
other  cases  of  amputation  a  simple  atrophy,  associated  with  a 
marked  decrease  in  tin  average  diameter  ol  the  nerve  fibers,  pre- 


Ranson,  Degeneration  in  Spinal  Nerves.  5 

sents  itself  with  striking  uniformity  (Vulpian  '68-'6c),  Erlen- 
meyer  '72,  Hayem  '76,  Dejerine  and  Mayor  '78,  Hayem  and 
Gilbert  '84,  Friedlander  and  Krause  '86,  Dudley  '86,  Rey- 
nolds '87,  Marinesco  '92,  Elzholz  '00,  on  human  material; 
and  Homen  '90,  Vanlair  '91,  Pilcz  '99,  on  animals).  The  mi- 
croscopical changes  are  of  some  importance.  The  individual 
fibers  are  much  decreased  in  size,  the  change  affecting  chiefly  the 
myelin  sheaths.  Many  of  the  fibers  are  entirely  devoid  of  myelin 
and  there  is  a  tendency  for  them  to  be  grouped  in  bundles.  These 
altered  fibers  have  been  interpreted,  sometimes  as  atrophied,  some- 
times as  regenerated  fibers;  but  the  former  interpretation  seems  to 
be  the  better  supported.  Of  the  authors  who  have  placed  them- 
selves on  record  with  regard  to  this  point,  six  regard  the  change  as 
an  atrophy,  while  four  believe  that  the  altered  fibers  represent  an 
attempt  at  regeneration;  and  on  the  side  of  the  majority  are 
included  the  two  most  thorough  investigations:  that  of  Fried- 
lander  and  Krause  ('86)  recording  eight  cases  of  amputation, 
and  that  of  Homen  ('90)  recording  experiments  on  more  than 
forty  dogs. 

As  a  typical  account  of  these  alterations  we  may  summarize  the 
description  given  by  Friedlander  and  Krause  ('86).  In  their 
eight  cases  the  nerve  stumps  presented  patches  of  normal  appear- 
ance separated  by  areas  entirely  devoid  of  medullated  fibers;  still 
other  areas,  constituting  the  larger  portion  of  the  cross-section 
contained  about  half  the  proper  number.  In  the  atrophied  bundles 
the  individual  fibers  are  about  one-third  their  normal  size,  and  may 
be  recognized  as  faint  refractile  rings,  which  do  not  take  the  Wei- 
gert  stain.  At  the  center  of  these  rings  a  barely  recognizable 
point  represents  the  remains  of  the  axis  cylinder. 

In  addition  to  this  simple  atrophy  there  occurs  in  the  proximal 
portion  of  some  of  the  severed  nerve  fibers  a  true  degeneration, 
not  distinguishable  histologically  from  Wallerian  degeneration. 
This  may  be  seen  in  Marchi  preparations  from  the  central  stumps 
of  experimentally  resected  nerves,  removed  twenty  to  forty  days 
after  the  operation  (Redlick  '93,  Moschaew  '93,  Biedl  '97). 
Some  observers  have  reported  negative  results  with  this  stain;  but 
it  must  be  remembered  in  this  connection  that  the  degeneration 
in  the  central  stump  occurs  about  fifteen  days  later  than  true  Wal- 
lerian degeneration  (Biedl  '97,  van  Gehuchten  '03),  and  that 
the  peripheral  degeneration  is  at  its  height  at  a  time  when   the 


6  'Journal  of  Comparative  Neurology  and  Psychology. 

alterations  in  the  central  stump  are  iust  beginning.  Too  early 
an  examination  of  the  material  may  thus  lead  to  erroneous  con- 
clusions. 

The  changes  in  the  ventral  root  are  less  marked  than  in  the 
mixed  nerve,  and  until  the  last  twenty  years  these  structures  were 
often  reported  normal  (Vulpian'68-'69,  Dickinson '68,  Dejerine 
and  Mayor  '78,  Dreschfeld  '79,  Friedlander  and  Krause 
"'86).  Atrophy  of  the  ventral  roots  was  reported  by  Berard  ('29), 
Turck  ('53),  Genzmer  ('76),  Hayem  and  Gilbert  ('84),  and 
Edinger  ('88);  and  during  the  last  two  decades  has  been  quite 
uniformly  observed  (Kahler  and  Pick  '80,  Reynolds  '87,  Mari- 
nesco  '92  and  Wille  '95).  According  to  Reynolds  the  atrophy 
is  due  to  an  increase  in  the  proportion  of  the  small  fibers,  while  in 
two  of  Wille's  cases  it  was  due  to  a  decrease  in  the  total  number. 
On  his  forty  dogs  Homen  found  a  decrease  in  the  ventral  root 
fibers  within  the  spinal  cord.  There  was  also  a  slightly  larger 
proportion  of  small  fibers  on  the  operated  than  on  the  normal  side. 
That  some  fibers  degenerate  and  disappear  from  the  ventral  roots 
after  the  section  of  the  mixed  nerves  has  also  been  demonstrated 
by  the  Marchi  reaction  in  animal  experiments  (Darkschewitsch 
'96,  Redlick  '93,  Moschaew  '93,  Cassirer  '98,  Ceni  '99,  VAN 
Gehuchten  '03). 

The  dorsal  roots  have  undergone  changes  very  similar  to  those 
in  the  ventral  roots;  the  authors  usually  describe  them  together 
and  in  identical  terms,  so  that  the  account  just  given  of  the  latter 
would,  with  the  following  exceptions,  serve  equally  well  for  the 
former.  Dickinson  ('68),  and  Friedlander  and  Krause  ('86) 
found  a  considerable  diminution  in  the  number  of  dorsal  root  fibers 
although  in  both  cases  the  ventral  roots  were  reported  practically 
normal.  Marinesco  ('92)  also  found  more  advanced  atrophy, 
and  Darkschewitsch  ('96)  more  degenerating  fibers  in  the  dorsal 
than  in  the  ventral  root.  The  roots  of  the  spinal  nerves  are  sub- 
ject to  considerable  normal  variation  in  size,  so  that  a  large  root 
might  suffer  considerable  atrophy  and  still  appear  normal;  and 
this  is,  no  doubt,  in  large  part  responsible  for  the  conflicting  state- 
ments to  be  found  in  the  literature. 

It  is  obvious  from  the  foregoing  account  that  the  roots  show  less 
pronounced  alterations  than  the  central  portions  of  the  severed 
nerve  trunks.  Friedlander  and  ECrause's  ('86)  statement  of 
this  relation  is  worth  some  attention.     We  have  already  described 


Ranson,  Degeneration  in  Spinal  Nerves.  J 

the  atrophic  nerve  fibers  which  these  authors  saw  in  the  central 
stumps  and  noted  that  they  considered  the  ventral  roots  normal, 
and  the  dorsal  roots  altered  only  to  the  extent  of  the  loss  of  a  small 
portion  of  the  fibers.  The  altered  elements  seen  in  the  nerve  were 
to  be  found  neither  in  the  ventral  nor  dorsal  roots.  But  within 
the  ganglia  and  especially  at  their  distal  extremities  before  the 
afferent  fibers  have  mixed  with  those  of  the  ventral  roots  the 
changes  are  seen  at  their  maximum;  hence  the  atrophy  seen  in  the 
nerve  stumps  affects  chiefly  the  peripheral  branches  of  the  T-pro- 
cesses.     This  has  recently  been  confirmed  by  Kleist  ('04). 

Asymmetry  of  the  spinal  cord  due  to  atrophy  of  the  correspond- 
ing halves  of  the  segments  associated  with  the  injured  nerves  is 
an  almost  constant  finding  (not  present  in  the  cases  reported  by 
Turck  '53  and  Friedreich  '73),  and  is  due  to  changes  in  both 
the  gray  and  the  white  substance.  The  only  change  in  the  white 
substance  which  occurs  with  sufficient  regularity  to  be  of  signifi- 
cance is  found  in  the  dorsal  funiculus;  atrophy  of  the  ventral  and 
lateral  funiculi  have  been  occasionally  reported.  (Atrophy  of 
the  ventral  funiculus,  Vulpian  '69  and  Kahler  and  Pick  '80;  of 
the  lateral  funiculus,  Switalski  '01;  atrophy  uniform  over  the 
entire  half  of  the  area  of  the  white  substance,  Leyden  '76, 
Dejerine  and  Mayor  '78.)  That  some  loss  of  substance  should 
occur  in  these  fiber  tracts  is  a  necessary  corollary  of  the  cell 
destruction  which,  as  we  shall  see,  occurs  in  the  ventral  and  dorsal 
cornua  and  in  Clarke's  column;  but  this  could  lead  to  only  a  very 
slight  atrophy.  It  is  more  probable  that  these  few  observations 
depend  upon  a  natural  asymmetry  of  the  cord  or  a  too  superficial 
examination  of  the  material.  Friedlander  and  Krause  ('86) 
state  that  in  many  of  their  preparations  it  seemed  as  if  the  entire 
half  of  the  cross-section  were  atrophied,  but  closer  study  showed 
that  the  loss  was  confined  to  the  gray  matter  and  the  dorsal  funi- 
culus. 

As  is  to  be  expected  from  its  anatomical  relations  with  the  atro- 
phied dorsal  roots,  the  dorsal  funiculus  shows  a  decrease  in  the 
area  of  its  cross-section  which  can  be  followed  cephalad  far  beyond 
the  segments  primarily  affected.  In  only  four  of  the  autopsy 
cases  was  it  reported  normal  (Vulpian  '69,  three  cases;  Fried- 
reich '73,  one  case).  In  some  instances  it  was  found  reduced  to 
two-thirds  its  original  dimensions.  To  explain  this,  Homen  ('90) 
asserts  that  the  individual  fibers  are  smaller  on  the  operated  side; 


8  'Journal  of  Comparative  Neurology  and  Psychology. 

but  on  the  other  hand  Friedlander  and  Krause  ('86)  state  that 
they  are  normal  and  that  the  atrophy  must  be  due  to  a  decrease  in 
their  number.  There  can  be  no  doubt  that  some  disappear  since 
the  Marchi  stain  reveals  a  certain  number  in  the  stages  of  dis- 
integration (human  material,  Flatau,  '97;  animal  material,  Mos- 
chaew  '93,  Cassirer  '98,  Ceni  '99).  The  degeneration  does 
not  appear  to  affect  more  than  a  small  part  of  the  fibers  of  the  funi- 
culus. 

In  all  the  cases  of  amputation  reported  since  1875  there  is 
essential  uniformity  as  regards  the  changes  in  the  ventral  cornu  on 
the  side  of  the  amputation  in  the  segments  associated  with  the 
injured  nerves.  The  area  of  the  cross-section  of  the  cornu  as  a 
whole  is  considerably  decreased,  sometimes  by  as  much  as  one- 
third  its  normal  dimensions.  The  number  of  motor  cells  has  been 
determined  in  a  number  of  cases  and  found  below  that  of  the  nor- 
mal side.  It  is  especially  the  dorsolateral  group  of  cells  that  is 
most  affected;  here  there  may  be  no  more  than  two-thirds  the 
original  number  (Marinesco  '92).  The  remaining  cells  are 
often  shrunken,  and  devoid  of  processes. 

In  none  of  the  amputation  cases  of  the  last  thirty  years  has  the 
dorsal  cornu  of  the  operated  side  been  reported  normal.  The  de- 
crease in  the  area  of  the  cross-section,  which  may  amount  to  one- 
half  the  original  area  (Switalski  '01,  case  4),  is  due  in  large  part  to 
the  loss  of  medullated  fibers  (Knope  '01).  The  substantia  gelati- 
nosa  and  the  column  of  Clarke  are  also  markedly  atrophied. 
The  decrease  in  the  size  of  the  column  of  Clarke  is  due  to  a  loss 
of  both  fibers  and  cells,  and  is  found  in  the  segments  some  distance 
removed  from  those  primarily  affected  (Friedlander  and 
Krause  '86,  Homen  '90,  and  others). 

By  far  the  most  interesting  point  for  us  is  the  lack  of  data  on  the 
spinal  ganglia;  most  observers  have  failed  to  take  any  note  of  them 
at  all,  or  have  overlooked  the  essential  changes.  Reynolds  ('87) 
found  an  increased  amount  of  connective  tissue.  Marinesco 
('92)  stares  that  although  many  nerve  fibers  had  disappeared  the 
spinal  ganglion  cells  were  intact.  That  these  are  the  only  in- 
stances where  the  spinal  ganglia  were  studied  in  the  autopsy 
cases  is  due,  no  doubt,  to  the-  difficulty  of  securing  these  structures 
in  the  hurry  of  the  autopsy  room. 

I  [OMEN  ('90),  in  his  extensive  series  of  animal  experiments,  gave 
ial  attention  to  this  subject,  but  failed  to  find  any  change  except 


Ranson,  Degeneration  in  Spinal  Nerves.  9 

an  atrophy  of  the  ganglion  as  a  whole  and  of  the  nerve  fibers  con- 
tained in  it.  There  seemed  to  be  some  atrophy  of  the  ganglion 
cells  but  of  this  Homen  could  not  be  sure.  He  did  not  consider 
the  possibility  of  a  decrease  in  the  number  of  cells.  Cassirer 
('98)  states  that  a  few  cells  in  all  probability  undergo  complete 
destruction.  He  says  that  the  question  of  the  loss  of  spinal  gan- 
glion cells  can  only  be  settled  by  resorting  to  an  enumeration. 
Thus  we  see  that  in  only  four  of  the  investigations  were  the  spinal 
ganglia  studied  and  even  in  these  cases  no  important  observations 
were  made. 

Some  additional  data  have  been  furnished  by  various  investiga- 
tions based  on  Nissl's  axonal  reaction.  After  cutting  the  sciatic 
nerve  near  its  exit  from  the  pelvis  in  a  number  of  dogs,  Lugaro 
('96),  found  that  not  all  the  cells  of  the  spinal  ganglion  showed  an 
equal  degree  of  chromatolysis,  a  fact  which  he  attributed  to  varia- 
tions in  the  resistance  of  the  individual  cells.  Thirty-nine  days 
after  the  operation,  there  was  a  manifest  diminution  in  the  number 
of  cells  and  an  abundant  proliferation  of  connective  tissue. 
Fleming  ('97),  who  performed  a  similar  operation  on  dogs  and 
rabbits,  found  a  decrease  in  size  of  the  spinal  ganglion  cells  soon 
after  the  operation.  Cell  destruction  is,  however,  slow  in  making 
its  appearance;  in  only  one  case  is  "disintegration  of  the  proto- 
plasm" noted  at  six  weeks;  after  18  weeks,  however,  many  cells 
have  disappeared.  Van  Gehuchten  ('97),  after cuttingthe  vagus 
in  rabbits,  observed  that  the  majority  of  the  nerve  cells  in  the  gan- 
glion nodosum  underwent  complete  degeneration  and  disappeared. 
He  believes  that  these  results  may  be  considered  typical  for  the 
spinal  as  well  as  for  the  cerebral  ganglia.  On  the  other  hand, 
Marinesco  ('98),  after  a  similar  operation  on  the  vagus  of  dogs, 
found  that  the  cells  in  the  ganglion  nodosum  passed  through  the 
phase  of  reaction  to  a  phase  of  restoration,  and,  therefore,  did  not 
undergo  complete  degeneration.  In  a  rabbit  six  months  after 
the  operation  he  could  not  find  the  cell  destruction  of  which  van 
Gehuchten  speaks.  Marinesco  also  regards  the  reaction  of 
the  vagus  as  typical  for  all  the  cerebro-spinal  ganglia.  Van 
Gehuchten's  observation  has  recently  received  support  from 
the  observations  of  Kosaka  and  Yogita  ('05),  who  found, 
fourteen  days  after  the  section  of  the  vagus  in  a  young  dog,  an 
almost  complete  disappearance  of  the  cells  of  the  ganglion  nodosum ; 
of  the  thousands  of  cells  only  sixty-five  remained. 


10          Journal  of  Comparative  Neurology  and  Psychology. 

Koster  ('03),  having  cut  the  sciatic  immediately  after  its  exit 
from  the  vertebral  canal  in  cats,,  dogs  and  rabbits,  found  that  all 
the  spinal  ganglion  cells  presented  alterations  of  their  tigroid 
bodies.  Onlv  a  part  of  these  cells  suffered  complete  degeneration 
and  this  occurred  for  the  most  part  after  the  284th  day.  The 
phase  of  repair  followed  the  chromatolysis  in  a  large  part  of  the 
cells  and  it  was  particularly  in  the  large  cells  that  the  restoration 
of  the  tigroid  substance  was  most  evident.  The  cells  that  sur- 
vived had  undergone  considerable  atrophy.  Kleist  ('04)  made 
his  experiments  on  half-grown  cats  and  rabbits,  cutting  some  of 
the  upper  cervical  or  lower  thoracic  nerves.  After  from  three  to 
six  months  a  large  proportion  of  the  spinal  ganglion  cells  (esti- 
mated at  33  per  cent.)  had  disintegrated  and  the  remaining  cells 
had  undergone  a  marked  atrophy. 

The  practical  bearing  of  this  problem  has  been  indicated  by 
ScHAFFER  in  his  Text-book  of  Physiology:  "If  the  observation 
of  van  Gehuchten  upon  the  nerve  cells  of  the  vagal  ganglion 
after  section  of  their  peripheral  fibers  is  correct,  and  is  a  phenom- 
enon of  general  occurrence,  it  is  difficult  to  see  how  the  sensory 
fibers  regenerate.  Restoration  of  function  in  such  cases  may, 
perhaps,  often  be  explained  by  the  ingrowth  of  sensory  nerve  fibers 
from  adjacent  areas  of  distribution." 

2.     Observations  on  the  Second  Cervical  Nerve  of  the  White  Rat. 

The  unsatisfactory  character  of  the  data  on  the  changes  in  the 
spinal  ganglia,  resulting  from  the  section  of  the  associated  nerves, 
emphasizes  the  necessity  of  some  further  investigation  along  this 
line,  and  in  the  experiments  now  to  be  described  special  attention 
was  given  to  determining  the  extent  of  cell  destruction  in  the  gan- 
glion. It  is  necessary,  by  way  of  preface,  to  state  a  few  of  the  essen- 
tial points  concerning  the  relation  of  the  spinal  ganglion  to  the 
afferent  fibers  of  the  nerve  and  dorsal  root.  We  may  safely  accept 
as  the  essential  element,  the  unipolar  cell  with  its  T-shaped  fiber, 
despite  the  fact  that  Nissl  ('03)  has  called  attention  to  some  facts 
that  point  to  another  view.  Nevertheless  there  are  many  cells  in 
the  ganglion  which  are  not  connected  with  medullated  fibers  in 
either  the  nerve  or  dorsal  root,  since  enumerations  show  that  the 
number  of  nerve  cells  in  the  ganglion  far  exceeds  that  of  the  med- 
ullated fibers  in  the  root  (Hatai  '02),  and  by  nearly  as  large  an 
amount  tin  number  of  medullated  afferent  fibers  in  the  peripheral 


Ranson,  Degeneration  in  Spinal  Nerves. 


II 


nerve  (Hardesty  '05).  Hatai,  working  on  the  white  rat,  ob- 
tained the  following  results  for  the  adult  specimen  of  167  gms. 
body  weight. 

table  1. 
Ratio  of  Spinal  Ganglion  Cells  to  Dorsal  Root  Fibers.       (Hatai,) 


Nerve.                    |     Number  of  Cells. 

Number  of  Fibers.              Ratio. 

VI  C.                                    12,20c 
IV  T                                    7,406 
II  L                                     9.442 

4,227 
1,522 
1,644 

1:  2.8* 
1:  4.8* 
1:  5.7 

*  The  figures  2.  7  and  4.  3  given  in  the  original  are  obviously  misprints. 

The  writer  in  studying  the  normal  relations  in  the  second  cervi- 
cal nerve  of  the  white  rat  has  obtained  results  confirmatory  of 
those  of  the  authors  already  mentioned.  In  the  three  cases  in 
which  the  dorsal  root  fibers  and  spinal  ganglion  cells  were  enumer- 
ated in  the  same  individual  nerve,  a  rather  constant  ratio  of 
approximately  I  fiber  to  3.2  cells  was  obtained.  The  first  two 
specimens  were  seventy-two  days  old  and  weighed  about  no  gms., 
the  third  was  six  months  old  and  weighed  188  gms. 


TABLE  11. 


Ratio   of    Spinal  Ganglion  Cells  to    Dorsal    Root    Fibers    in     the 
Cervical  Nerve  of  the  White  Rat. 


Second 


Specimen. 

Number  of  Cells. 

Number  of  Fibers. 

Cells  per  Fiber. 

6  months  old     .  .  . 

7,72i 
8,116 
8,624 

2,472 

2>394 
2,689 

3-i 

3-3 
3-2 

These  results  are  corroborative  of  those  obtained  by  earlier 
observers.  The  number  of  cells  in  a  given  spinal  ganglion  is 
about  three  times  greater  than  the  number  of  medullated  fibers 
in  the  corresponding  root.  .  Without  going  into  a  discussion  of 
the  significance  of  this  relation,  it  may  be  said  that  it  is  the  large 
cells  of  the  ganglion  which  alone  are  associated  with  medullated 
fibers  (Dogiel  '96,  Hatai  '02).  According  to  this  view,  70 
per  cent,  of  the  cells  in  the  second  cervical  spinal  ganglion 
of  the  white  rat  are  small  cells  not  associated  with  any  medullated 
fibers  which  would  be  cut  in  dividing  the  peripheral  nerve.  It  is 
obvious  that  these  facts  must  have  an  important  bearing  on  the 
results  of  injury  to  the  nerve. 


12  Journal  of  Comparative  Neurology  and  Psychology. 


It  is  also  important  to  note  that  the  number  of  medullated  dorsal 
root  fibers  is  constantly  increasing  in  the  growing  animal  (Hatai 
*02).  In  the  second  cervical  root  of  the  white  rat  at  twelve  days 
of  age  the  number  of  medullated  fibers  is  less  than  that  given  in 
Table  II,  which  represents  the  number  in  rats  seventy-two  days 
old.  In  two  rats  twelve  days  old  thenumberof  medullated  dorsal 
root  fibers  was  found  to  be  1608  and  1521,  respectively.  Hence, 
when  the  nerve  is  cut  in  animals  of  this  age,  even  fewer  medullated 
fibers  are  injured  than  would  be  the  case  in  the  adult  animal. 

It  should  also  be  mentioned  that  the  number  of  dorsal  root  fibers 
may  be  taken  as  a  fair  indication  of  the  number  of  afferent  fibers 
in  the  peripheral  nerve,  the  "distal  excess"  (Hardesty  '05)  not 
being  very  large  in  this  nerve  of  the  rat.  Table  III  shows  that 
the  ventral  and  dorsal  rami  of  the  nerve  contain  only  8  percent, 
or  10  per  cent,  more  fibers  than  are  found  in  the  ventral  and  dorsal 
roots.  It  is,  therefore,  not  misleading  to  use  the  number  of  dorsal 
root  fibers  as  an  index  of  the  afferent  fibers  in  the  peripheral  nerve. 

TABLE  III. 
Showing  the  Distal  Excess  in  the  II   C.   Nerve  of  the  Adult  White  Rat. 


Weight. 

Ventral 
Root. 

Dorsal 
Root. 

Sum  of 
Roots. 

Distal 
Excess. 

Percentage 
of  D.  E. 

Sum  of 
Rami. 

Ventral 
Ramus. 

Dorsal 
Ramus. 

302  gms. 
161   gms. 

646 
672 

2,386 
2,090 

3,032 
2,762 

257 
276 

8 
10 

3,289 
3,098 

887 
708 

2,402 
2,390 

The  present  studies  were  carried  out  on  white  rats  in  which 
the  second  cervical  nerve  of  the  right  side  had  been  divided. 
Sonic- animals,  operated  on  when  twelve  days  old,  were  allowed  to 
live  for  two  months,  others  for  four  months;  the  nerve  was  also 
cut  in  adult  rats  which  were  allowed  to  survive  the  operation  four 
months.  A  numerical  analysis  was  then  made  of  the  spinal  gan- 
glion and  of  the  ventral  and  dorsal  roots  of  the  injured  nerves,  in 
order  to  determine  to  what  extent  degenerative  changes  had  taken 
place  and  what  amount  of  repair,  if  any,  had  occurred. 

Technique.— In  operating  upon  white  rats  twelve  days  of  age 
it  is  necessary  to  work  rapidly  and  to  conserve,  as  far  as  possible, 
the  body  temperature.  The  little  rat  was  held  in  position  in  the 
hands  ol  an  assistant  with  its  neck  slightly  stretched  and  head 
bent  forward.  An  incision  was  made-  in  the  midline  on  the-  back 
ot  tin    neck,  with  the  atlas  at  its  middle  point,  and  carried  down- 


Ranson,  Degeneration  in  Spinal  Nerves.  13 

ward  through  the  ligamentum  nucha?  until  the  tuberculum  poste- 
rius  of  the  atlas  was  uncovered.  The  integument  and  long'muscles 
of  the  neck  were  held  aside  by  a  spring  retractor  inserted  through 
the  median  incision.  The  caudal  margin  of  the  atlas  then  served 
as  a  guide  to  the  point  where  the  right  second  cervical  nerve 
emerges  from  the  vertebral  canal.  A  short  stretch  of  the  nerve1 
was  laid  bare  and  cut  with  sharp  scissors  about  1  mm.  from  the 
ganglion.  No  part  of  the  nerve  was  resected  and  its  central  and 
peripheral  ends  were  held  in  close  proximity  by  the  mass  of  tissue 
in  which  they  were  imbedded. 

All  blunt  dissection  was  avoided;  sharp  instruments  were  used 
throughout,  so  that  the  tissues  suffered  a  minimum  amount  of 
injury.  It  was  not  practicable  to  close  the  wound  with  deep 
sutures  in  the  rats  twelve  days  old,  but  this  was  done  when  the 
operation  was  performed  on  adult  rats.  The  skin  incision  was 
closed  with  a  collodion  dressing. 

Were  it  not  for  the  fact  that  a  standard  objection  to  results  ob- 
tained in  this  way  is  that  they  are  due  to  a  septic  infection,  the 
reader  might  be  spared  the  usual  paragraph  on  asepsis.  ,  Under 
the  circumstances,  however,  some  details  must  be  given.  The 
skin  of  the  animal's  neck,  after  it  had  been  freed  from  hair,  was 
thoroughly  cleaned  with  ether-alcohol  to  remove  oily    deposits 

1Only  the  dorsal  division  of  the  nerve  was  cut;  the  ventral  division,  which  is  much  smaller,  was  not 
injured.  This  turns  abruptly  ventralward  just  distal  to  the  spinal  ganglion  and  was  quite  out  of  the 
field  of  the  operation.  In  order  to  form  some  idea  of  what  proportion  of  the  afferent  fibers  were  severed 
in  cutting  the  dorsal  ramus  it  is  necessary  to  know  the  relative  size  of  the  two  branches.  In  two  cases 
studied,  the  proportion  of  fibers  was  as  follows: 

Specimen.  Dorsal  Ramus.      Ventral  Ramus.  Ratio. 

9  months,  302  gms.  2,402  887  1 12.7 

4  months,  161  gms.  2>39°  7°8  I:3-3 

The  dorsal  division  is  thus  seen  to  be  much  the  larger.  It  is  mainly  sensory  since  it  forms  the  N. 
occipitalis  major,  which,  after  giving  off  a  few  muscular  twigs,  goes  to  the  skin  on  the  back  of  the  head. 
The  ventral  division  goes,  in  large  part,  to  the  muscles  about  its  origin,  only  a  small  twig  going  to  join 
the  common  trunk  of  the'N.  auricularis  magnus  and  N.  cutaneus  colli  which,  in  the  rat,  is  formed 
chiefly  by  the  ventral  division  of  the  third  nerve.  . 

From  these  data  we  may  roughly  estimate  that  about  13  per  cent,  of  the  afferent  fibers  of  the  second 
nerve  go  by  way  of  the  ventral  branch  and  were  not  affected  by  the  operation.  This  figure  is  obtained 
by  regarding  the  ventral  branch  as  a  purely  muscular  nerve,  which  according  to  Sherrington's  ('94) 
observations  should  be  composed  of  afferent  and  efferent  fibers  in  the  ratio  of  2  to  3.  This  would  give 
about  350  afferent  fibers  in  the  ventral  branch,  which,  allowing  for  a  10  per  cent,  distal  excess,  would 
leave  315  represented  in  the  dorsal  root.  The  average  number  of  dorsal  root  fibers  in  these  two  nerves 
was  2238,  of  which  the  315  going  to  the  ventral  branch  would  constitute  about  13  per  cent. 


I4         Journal  of  Comparative  Neurology  and  Psychology. 

and  was  then  washed  with  a  solution  of  mercuric  chloride  and 
left  covered  with  a  pad  moistened  in  that  solution,  while  the 
operator  cleansed  his  hands.  From  this  point  on,  the  operator's 
hands  touched  nothing  but  the  sterile  instruments  laid  out  on  a 
sterile  tray;  all  other  things  were  handled  by  an  assistant.  Noth- 
ing touched  the  wound  but  the  sterile  instruments  and  sponges; 
the  wound  was  too  small  to  permit  of  introducing  the  fingers  for 
any  purpose. 

Thanks  to  the  natural  resistance  of  the  animals,  as  well  as  to 
the  care  taken  to  preserve  the  vigor  of  the  tissues  by  the  use  of 
sharp  instruments  and  hot  sponges,  the  aseptic  precautions  were 
efficient,  and  not  in  a  single  case  was  there  any  sign  of  infection. 
(In  one  animal  the  collodion  dressing  came  off  after  four  days,  but 
this  one  was  at  once  discarded.)  As  final  evidence  that  sepsis  has 
nothing  whatever  to  do  with  the  results  of  these  experiments,  it 
may  be  said  that  in  a  series  of  animals  killed  five,  six,  seven,  eight, 
twelve,  seventeen  and  twenty  days  after  the  operation,  the  wound 
was  found  in  perfect  condition;  and  a  microscopical  study  of  the 
ganglion  and  nerve  stump  stained  with  toluidin-blue  failed  to 
show  any  indications  of  infection. 

At  the  autopsv,  note  was  made  of  the  size  of  the  neuroma  and 
of  any  regeneration  that  had  occurred.  The  operated  nerve  was 
then  carefully  dissected  out  together  with  its  neuroma,  ganglion, 
and  roots,  straightened  out  on  a  piece  of  card-board,  and  fixed  in 
I  per  cent,  osmic  acid.  The  left,  or  normal  nerves,  were  treated 
in  the  same  manner  as  the  right;  but  they  were  not  used  in  the 
determination  of  the  norm,  since  it  was  theoretically  possible  that 
their  condition  might  in  some  way  be  influenced  by  the  injurv 
inflicted  on  the  nerve  of  the  opposite  side.  And,  as  a  matter  of 
fact,  such  a  crossed  degeneration  has  been  reported  in  the  ventral 
root  fibers  (Braeunig  '03).  For  this  reason  it  was  considered 
safer  to  take  the  control  material  from  entirely  normal  animals. 

After  fixation  in  1  per  cent,  osmic  acid,  the  tissue  was  imbedded 
in  paraffin  and  cut  into  transverse  sections.  The  sections  of  the 
roots  were  3/*  to  4  /x  thick;  those  of  the  ganglion  were  1 2  //thick  and 
arranged  in  serial  order.  When  a  perfect  series  through  the  gan- 
glion was  nor  obtained  the  specimen  was  discarded. 

I  he  osmic  acid  not  only  stains  the  myelin  of  the  nerve  fibers, 
bur  also  brings  out  the  nerve  cells  so  well  that  no  further  treatment 
is  necessary.      1  he  technique  of  counting  nerve  fibers  and  spinal 


Ranson,  Degeneration  in  Spinal  Nerves.  15 

ganglion  cells  has  been  described  in  a  number  of  papers  from  this 
laboratory,  and  especially  in  the  publications  of  Hardesty.  In 
counting  fibers  the  net  method  was  used.  The  entire  ventral 
root  and  each  of  the  fasciculi  of  the  dorsal  root  and  mixed  nerve  were, 
with  few  exceptions,  small  enough  to  come  within  one  field  of  the 
microscope.  The  field  was  divided  into  small  squares  by  a  net 
micrometer  placed  in  the  ocular.  The  fibers  in  each  square  were 
counted  in  the  order  of  the  squares  until  the  enumeration  of  the 
entire  root  or  fasciculus  was  completed.  The  counting  was  done 
automatically  by  pressing  the  lever  of  a  counting  machine  once 
for  each  fiber  and  reading  off  the  final  number  from  the  face  of 
instrument.  In  the  few  cases  in  which  it  was  necessary  to  shift 
the  preparation  during  the  enumeration  of  a  root  or  fasciculus, 
a  straight  line  joining  two  prominent  points  was  regarded  as  the 
limit  between  the  two  fields,  and  the  position  of  this  line  was 
indicated  by  a  line  of  the  micrometer  made  to  lie  across  the  two 
points. 

The  enumeration  of  the  nerve  cells  in  the  serial  sections  of  the 
spinal  ganglia  was  somewhat  more  difficult,  since  several  suc- 
cessive sections  may  contain  parts  of  the  same  cell.  The  diffi- 
culty was  avoided  by  counting  in  a  given  section  only  those  cells 
which  showed  nucleoli.  These  structures  are  small  enough  to 
escape  division  by  the  knife  and  so  to  lie,  in  the  vast  majority  of 
the  cases,  within  the  plane  of  a  single  section.  In  most  cases  each 
cell  has  but  one  nucleolus,  in  rare  instances  there  are  two;  but  the 
presence  of  a  pair  would  lead  to  error  only  in  those  extremely  rare 
instances  when  the  knife  passed  between  them  in  such  a  way  as  to 
give  a  nucleolus  to  each  of  two  sections  of  the  same  cell.  Har- 
desty estimates  that  this  would  not  give  an  error  of  more  than 
0.2  per  cent.  The  cells  with  nucleoli  were  enumerated  with  the 
aid  of  the  counting  machine  in  each  section  of  the  series;  the  sum 
of  the  numbers  for  the  individual  sections  gave  the  total  for  the 
ganglion.  Since  a  section  of  the  ganglion  could  not  all  be  brought 
into  the  field  at  once,  it  was  necessary  to  use  a  mechanical  stage 
which  permitted  a  ready  shifting  of  the  preparation.  In  the  spinal 
ganglion  the  different  portions  of  the  section  are  so  character- 
istic that  one  does  much  better  to  dispense  with  the  net  micrometer 
and  depend  entirely  upon  the  natural  markings,  which  are  ade- 
quate to  prevent  confusion  as  to  what  part  of  the  section  has  been 
counted. 


16  Journal  of  Comparative  Neurology  and  Psychology. 

Results. — The  results  of  the  present  investigation  may  all  be 
summarized  in  the  following  table: 


table  rv. 


Showing  the  Numerical  Relations  of  the  II  C.  Nerve  of  the  White  Rat  in  the 
Normal  Condition  and  after  Section  of  the  Ramus  Posterior  just  Distal  to 
the  Ganglion. 


Specimens. 


(0 

(2) 
(3) 
(4) 
(5) 


Xcrmal  Rats. 

-2  days  old  (normal)    

72  days  old  (normal) 

72  days  old  (normal) 

72  days  old  (normal) 

72  days  old  (normal) 

(6)  240  days  old,  left  (normal)  . .  . 

(7)  240  days  old,  right  (normal)  . . . 
Rats  Operated  on  at    12    Days    of  Age 

and  Killed  after  60  Days. 

(8)  72  days  old  (operated) 

(9)  72  days  old  (operated) 


(10)  72  days  old  (operated)  1 10* 

(11)  72  days  old  (operated) 1  io* 

(12)  72  days  old  (operated) no* 

Rats  Operated  on  at   12   Days  of  j. 

and  Killed  after  120  Days. 

(13)  132  days  old  (operated) 274 


Body  Gan-     Ventral    Dorsal 

Weight       glion"        Root         Root 
in  gms.      Cells-    Fibers.     Fibers. 


no* 
no* 

155 

110* 

no* 


no 
no* 


(14)  132  day  sold  (operated)  140 

(15)  132  days  old  (operated) 

Rats  Operated  on  at   140  Days  of   Age 

and  Killed  1 20  Days  Later. 

(16)  260  days  old  (operated)  

(17)  260  days  old  (operated) 

(18)  26odaysold  (operated) 


7,721 
8,116 

9-343 


8,624 


3,845 
3,896 

3,764 
4,193 
4,497 


4,020 


660 

590 

59i 

703 

773 
523 


537 
506 

43' 


5»5 


2,472 
2,394 

1,959 
2,217 


2,641 


1,236 
1,983 
1,607 


'-455 


Neuroma 


Regen- 
era- 
tion-. 


large 
large 


partial 
none 


very  small       none 
medium        partial 
large  partial 


'  146 

4,516 

646 

2,357 

16, 

— 

562 

1,987 

225 

4,215 

610 

1,983 

302 

— 

630 

2,176 

264 

4,176 

506 

2,219 

large 
very  snia 


partial 
(  quite 
j    perfect 
small  partial 


large  none 

small      very  slight 
large  none 


The  weights  marked  with  a  star(*)  have  been  calculated  from  the  age,  no  record  having  been  taken 
of  the  body  weight  in  these  cases. 

I.     Changes  Produced  by  Section  of  the  Nerve    in    Young    Rats. 

1  he  most  interesting  of  the  observations  to  be  recorded  in  this 
place  concerns  the  pronounced  cell  destruction  that  occurred  in 


Ranson,  Degeneration  in  Spinal  Nerves.  ij 

the  spinal  ganglion;  the  extent  and  constancy  of  the  degeneration 
is  expressed  in  Table  V. 

table  v. 
Showing  the  Decrease  in  the    Number  of  Cells    in  the    Spinal  Ganglion  Sixty 
Days  After  the  Division  of  the  Ramus  Posterior  of  the  II  C.    Nerve  in  Rats 
Twelve  Days  Old. 

Normal.  Operated. 

7,7^1  3>845 

8,116  3,896 

9,343  3>764 

8,624  4,193 

4,497 
4)33,804  5)20,195 

Average 8,451  4,°39 

Average  loss   4,412. 

Per  cent,   average  loss 52 

From  Table  V  we  see  that  two  months  after  the  second  cervical 
nerve  had  been  cut  in  a  rat  twelve  days  old  the  corresponding 
spinal  ganglion  had  lost  about  one-half  its  cells,  and  that  this 
occurred  with  striking  uniformity  in  five  different  specimens.  In- 
deed, we  find  that  the  smallest  number  of  cells  in  the  operated 
ganglia,  3764,  differs  from  the  largest  number  4497  by  only  19  per 
cent,  of  the  smaller  number,  while  in  the  normal  ganglia  the  great- 
est variation  amounts  to  21  per  cent.  Hence  there  can  be  little 
doubt  but  that  the  numerical  differences  which  the  operated  gan- 
glia show  among  themselves  are  due  to  normal  individual  variation 
present  in  the  ganglia  before  the  operation.  We  repeat,  there- 
fore, that  this  table  shows  an  altogether  striking  uniformity  in  the 
number  of  cells  in  the  operated  ganglia,  and  that  the  number  of 
cells  dropping  out  of  a  ganglion  must  represent  a  certain  constant 
percentage  of  the  cells  it  originally  contained.  There  must  be 
some  very  definite  reason  for  this  constant  reaction;  but  our  knowl- 
edge of  the  architecture  of  the  spinal  ganglion  is  at  present  so 
vague  that  it  is  not  possible  to  say  what  are  the  responsible  factors. 

If  it  is  desired  to  know  the  percentage  of  cells  that  disappear, 
this  may  be  determined  by  taking  the  average  normal  number  of 
cells,  8451,  as  the  base  number,  of  which  4412,  the  average  num- 
ber of  cells  destroyed,  constitutes  52  per  cent.  Here  again  we 
are  totally  at  a  loss  for  an  explanation.  We  know  of  no  anatomical 
relations  which  would  justify  the  expectation  of    such    a    result. 


l8  'Journal  of  Comparative  Neurology  an  J  Psychology. 

The  number  of  medullated  afferent  nerve  fibers  cut  in  the  opera- 
tion on  a  twelve- day  old  rat  is  about  1500.  [The  average  number 
of  medullated  fibers  in  the  dorsal  roots  of  twelve-day  old  rats  was 
found  to  be  1568  (p.  274);  to  this  must  be  added  a  10  per  cent, 
"distal  excess"  to  find  the  number  of  medullated  afferent  fibers  in 
the  nerve  (p.  274);  and  from  this  result  13  percent,  must  be  sub- 
tracted for  the  afferent  fibers  running  in  the  uninjured  ramus 
anterior  (p.  275).  This  calculation  gives  1500  medullated  afferent 
fibers  which  would  be  injured  at  the  operation.]  And  were  all  the 
cells  associated  with  these  1500  fibers  to  drop  out,  the  loss  would 
only  amount  to  17  per  cent.  Or,  expressed  in  other  words,  nearly 
three  times  as  many  cells  have  disappeared  as  can  be  accounted  for 
in  terms  of  medullated  axons  injured  at  the  time  of  the  operation. 
Even  if  we  assume  that  all  the  axons  ever  to  develop  are  present 
(partly  as  non-medullated  fibers)  at  the  time  of  the  operation  on 
the  young  rat,  and  if  we  let  this  be  represented  by  the  number  of 
medullated  afferent  axons  in  the  adult  nerve,  we  find  that  even  this 
number,  which  does  not  exceed  2500  (see  p.  274)  is  inadequate  to 
account  for  the  number  of  degenerated  cells.  For  the  explanation 
of  these  results  we  are,  therefore,  forced  to  fall  back  upon  the 
existence  of  some  as  yet  unknown  relations  within  the  spinal 
ganglion. 

There  was  not  sufficient  disturbance  of  the  blood  supply  to  ac- 
count for  the  degeneration,  since  the  artery  and  vein  accompany- 
ing each  root  were  not  in  any  way  injured.  The  objection  that 
the  degeneration  was  due  to  a  septic  infection  has  been  answered 
in  connection  with  the  discussion  of  the  technique,  and  against 
such  an  objection  there  also  speaks  the  fact  that  infection  could 
nor  produce  such  uniform  results. 

It  might  be  supposed  that  the  fact  that  only  the  dorsal  branch 
was  cut  and  the  ventral  branch  left  intact  explained  the  occurrence 
of  a  partial  degeneration,  and  that  if  both  branches  had  been  cut 
all  the  cells  would  have  disappeared.  This  supposition  is,  how- 
ma  nifestly  incorrect  since  the  intact  ventral  branch  did  not 
contain  more  than  1 3  per  cent,  of  the  afferent  fibers  (see  footnote, 
p.  275),  and  hence  cannot  be  responsible  for  the  48  per  cent,  of  the 
cells  which  survive. 

I  he  results  obtained  by  the  enumeration  of  the  medullated  nerve 
fibers  in  the  ventral  and  dorsal  roots  of  young  rats  surviving  two 
months  after  the  section  of  the  second  cen  ical  nerve  are  much  less 


Ranson,  Degeneration  in  Spinal  Nerves. 


J9 


constant.  The  percentage  of  loss  is  much  smaller  than  in  the 
case  of  the  ganglion  cells,  scarcely  greater  than  the  percentage  of 
individual  variation,  so  that  the  latter  tends  to  render  the  former 
less  evident.  But  this  consideration  only  in  part  explains  the  lack 
of  uniformity  in  the  results;  it  seems  that  the  degenerative  pro- 
cesses in  the  root  fibers  are  more  variable  than  those  in  the  ganglion 
cells  and  more  directly  dependent  upon  such  conditions  as  reunion 
of  the  central  and  peripheral  stump  of  the  nerve. 

TABLE  VI. 

Showing  the  Decrease  in  the  Number  of  the  Medullated  Nerve  Fibers  in  the 
Ventral  and  Dorsal  Roots  Two  Months  After  the  Section  of  the  Ramus 
Posterior  of  the  II  C.  Nerve  in  Rats  Twelve  Days  Old. 

(Normal  and     Operated"  Material  from  Different  Animals.) 


Ventral  Root. 

Dorsal  Root. 

Normal. 

Operated. 

Normal. 

Operated. 

689 

660 

590 
591 

523 
537 
506 

43 1 

2,472 
2,394 
i,959 
2,217 

2,641 
1,236 
1,983 
1,607 

Sum 

Average 

M3° 
632.5 

i,997 
499.2 

9,042 
2,260.5 

7,467 
1,866.7 

Average   loss 1 33 .3 

Average  (%)  loss 21 


393-* 
17 


The  ventral  roots  show  a  fairly  uniform  loss  of  fibers.  The 
smallest  number  of  fibers  in  the  normal  roots  (590)  exceeds  by  53 
the  largest  number  in  the  operated  roots  (537).  Moreover,  the 
average  of  the  operated  roots  falls  133  behind  the  average  for  the 
normal  roots,  making  an  average  loss  of  21  per  cent.  This  loss 
is,  however,  by  no  means  so  uniform  as  that  in  the  number  of 
spinal  ganglion  cells.  The  loss  of  fibers  in  the  ventral  root  is  in 
harmony  with  the  results  reported  by  numerous  investigators  who 
found,  as  a  result  of  cutting  the  peripheral  nerve,  fibers  present 
in  the  ventral  root  which  gave  the  Marchi  reaction  (p.  268).  It 
is  also  a  necessary  result  of  the  degeneration  of  the  cells  of  the 
ventral  cornu  of  the  spinal  cord  so  constantly  found  after  the 
section  of  nerves  (p.  270). 

Even  more  variability  is  shown  in  the  column  of  Table  VI  repre- 
senting the  operated  dorsal  roots.  The  first  operated  dorsal  root 
that  was  subjected  to  an  enumeration  contained  2641  nerve  fibers, 


20       '  'Journal  of  Comparative  Neurology  and  Psychology . 

a  number  even  greater  than  the  normal  average  for  rats  of  that 
age.  The  other  three  roots  fall  below  the  normal;  in  one  case  the 
number  goes  as  low  as  1236.  The  average  loss  is  393  fibers  or 
17  per  cent. 

The  deficiencv  of  fibers  in  the  dorsal  roots,  associated  with  the 
injured  nerves,  finds  its  counterpart  in  the  degenerating  fibers 
which  may  be  recognized  bv  the  method  of  Marchi  (see  p.  267). 
According  to  recorded  observations  the  degenerating  fibers  con- 
stitute  only  a  fraction  of  the  total  number.  To  what  extent  de- 
generation occurred  in  our  specimens  can  only  be  determined  by 
study  of  the  roots  with  the  Marchi  method,  because  it  is  not  possi- 
ble to  say  what  part  of  the  fibers,  enumerated  in  this  investigation 
have  been  formed  since  the  operation  as  an  attempt  to  repair  the 
damaged  root. 

TABLE  VII. 

Showing  the  Relation  of  the  Number  of  Dorsal  Root  Fibers  to  Spinal  Ganglion 
Cells  in  the  Operated  II  C.  Nerve  of  the  White  Rat. 


Specimen-. 

Spimal   Ganglion 
Cells. 

Dorsal  Root 
Fibers. 

Ratio. 

Rat     8 

3.^45 
3.764 
4,193 
4.497 

2,641 
1,236 
1,983 

1 ,607 

1:1.4 
1:3.0 
1:2.1 

Rat    12 

1:2.7 

Average  of  3  nor- 
mal rats  (Table  II) 

8.153 

2,485 

1:3.2 

Table  VII  shows  that  in  every  case  there  are  more  than  enough 
spinal  ganglion  cells  to  account  for  the  dorsal  root  fibers,  although 
in  one  case  the  excess  of  cells  is  not  very  great.  By  comparison 
with  the  average  normal  ratio  taken  from  Table  II,  it  will  be  seen 
that  the  ratio  of  cells  to  fibers  is  reduced  in  the  operated  nerves, 
and  that  while  in  the  normal  nerve  it  is  approximately  constant 
at  one  fiber  to  32  cells  in  the  operated  nerves  it  shows  much  greater 
variation.  1  lie  table  also  shows  that  there  is  no  constant  relation 
between  the  number  oJ  spinal  ganglion  cells  destroyed  by  the  opera- 
tion and  the  number  of  dorsal  root  fibers  which  are  found  two 
months  later;  and  that,  therefore,  the  loss  of  dorsal  root  fibers 
cannot,  without  some  qualification,  be  attributed  to  the  degener- 


Ranson,  Degeneration  in  Spinal  Nerves. 


21 


ation  in  the  spinal  ganglion.     The  possible  factors  which  may 
complicate  the  result  are  given  in  the  footnote,  on  p.  275. 

II.     The  Influence  of  the  Length    of    the    Post-operative    Period 

upon  the  Results. 

After  the  changes  just  described  had  been  found  in  the  rats  that 
had  survived  the  operation  for  two  months,  the  question  arose 
whether  the  degeneration  had  come  to  an  end  before  the  animal 
was  killed,  and  whether  if  the  rat  were  allowed  to  live  for  a  longer 
period  of  time,  further  changes  might  not  take  place.  It  was 
thought  possible  that  the  number  of  spinal  ganglion  cells  might 
further  decrease,  and  that  the  roots  might  either  continue  to  lose 
fibers,  or  perhaps  show  a  tendency  to  repair. 

TABLE  VIII. 

Showing  the  Numerical  -Relations  in  the  II  C.  Nerve  in  Rats  which  Lived  Four 
Months  after  Section  of  the  Ramus  Posterior  of  that  Nerve  when  the  Animals 
were  Twelve  Days  Old. 


Spinal  Ganglion 
Cells. 

Ventral  Root 
Fibers. 

Dorsal  Root 
Fibers. 

4,020 
4,516 

5r5 
646 

562 

M55 
*»357 

1,987 

4,268 

574 

J>933 

TABLE  IX. 


Showing  the  Influence  of  the  Lapse  of  Time  upon  the  Effect  of  Cutting  the 

II  C.  Nerve.1 


Average  Number  of 


Ganglion  Cells 

Ventral  Root  Fibers. 
Dorsal  Root  Fibers.  . 


2  Months  After  the 
Operation. 


(5)  4.039 
(4)  499 
(4)  1,866 


4  Months  After  the 
Operation. 


(2)  4,268 

(3)  574 
(3)  x>933 


JThe  figures  in  parentheses  indicate  the  number  of  cases  from  which  the  averages  were  obtained. 

From  Table  IX  we  see  that  the  number  of  spinal  ganglion  cells, 
although  still  far  below  the  normal,  is  a  little  greater  in  the  speci- 
mens removed  after  four  months  than  in  those  removed  after  two 


22         Journal  of  Comparative  A  eurology  and  Psychology. 

months.  According  to  our  present  knowledge  there  is  no  reason 
to  expect  any  regeneration  of  the  spinal  ganglion  cells.  This  state- 
ment is  based  in  part  on  Hatai's  (02)  study  of  the  growth  changes 
in  the  spinal  ganglia,  but  more  particularly  on  the  negatiye  results 
of  a  series  of  investigations  undertaken  for  the  purpose  of  testing 
the  regenerative  capacity  at  one  time  supposed  to  belong  to  these 
structures  (Tirelli  '95,  Monti  and  Fieschi  '95).  The  slight 
excess  of  cells  in  the  four-month  specimens  is  probably  of  no  sig- 
nificance, representing  nothing  more  than  the  individual  variation 
ot  which  so  much  has  already  been  said.  Further  support  is  given 
to  this  view  bv  the  fact  that  of  the  two  specimens  enumerated  the 
first  gives  a  figure  close  to  the  average  for  the  two-month  specimens 
while  the  second  runs  much  higher  and  in  all  probabilty  represents 
a  large  ganglion  which  originally  contained  over  9000  cells. 

The  point  of  importance  is  not  that  there  is  a  slight  excess  of 
cells  in  the  four-month  specimens,  but  that  there  is  certainly  no 
decrease,  and  that,  therefore,  the  process  of  cell-destruction  runs  a 
rather  rapid  course  and  is  completed  during  the  first  two  months, 
after  which  there  is  no  further  change.  This  is  of  interest  in  con- 
nection  with  the  usual  doctrine  that  in  chromatolysis  the  phase 
of  reaction  is  followed  by  a  phase  of  restitution,  which  may  result 
in  the  complete  restoration  of  the  cell,  or  may  in  turn  give  place 
to  a  phase  of  degeneration,  resulting  in  the  gradual  disappearance 
of  the  injured  neurones.  It  is  obvious  that  in  this  case  the  phase 
of  degeneration  (if  it  can  properly  be  separated  as  a  distinct  phase 
at  all)  must  have  been  a  rapid  one  which  came  to  a  definite  ter- 
mination. It  did  not  result  in  the  destruction  of  cell  after  cell  until 
all  had  disappeared.  According  to  recent  observations  of  Koster 
('03),  who  cut  the  sciatic  nerve  in  cats,  rabbits  and  dogs,  the  cell 
destruction  in  the  spinal  ganglia  is  only  slightly  noticeable  after 
100  days,  but  is  very  marked  after  284  days.  There  can  be  no 
doubt  that  in  my  experiments  on  rats  the  degeneration  was  com- 
plete  before  the  end  of  the  first  sixty  days.  That  my  animals 
very  young  and  of  a  different  zoological  order  from  those  of 
Kosti  R,  may  in  parr  explain  the  discrepancy  in  the  results.  It 
should  be  mentioned,  however,  that  Koster  did  not  control  his 
observations  by  an  actual  enumeration  of  the  cells. 

By  reference  to  Table  IX  it  will  be  seen  further  that  the  number 
of  ventral  root  fibers  is  greater  in  the  animals  which  survived  four 
months  than  in  those  which  were  killed  at  an  earlier  date.      The 


Ranson,  Degeneration  in  Spinal  Nerves.  23 

difference,  howeve  amounts  to  only  15  per  cent,  of  the  smaller 
number,  and  this  can  readily  be  accounted  for  in  terms  of  normal 
growth.  There  seems,  therefore,  to  be  little  if  any  tendency  to 
repair  the  ventral  roots  in  the  sense  of  an  acceleration  of  the  nor- 
mal rate  of  fiber  formation  to  compensate  for  a  previous  loss.  Of 
course  the  neurones  represented  by  the  degenerating  fibers  in  the 
root  undergo  complete  destruction  (p.  270)  and  no  regeneration 
of  the  injured  axons  could  be  expected.  But  it  was  deemed  possi- 
ble that  some  reserve  cells  might  be  located  in  the  ventral  cornua, 
which  might  take  part  in  a  reformation  of  the  ventral  root  after 
the  neurones  whose  axons  originally  entered  into  its  formation  had 
been  destroyed.  There  is  no  evidence  that  such  a  compensatory 
process  occurred  in  this  set  of  experiments;  and  if  reserve  cells  are 
present  in  the  ventral  cornua  of  the  spinal  cord,  they  certainly  failed 
to  respond  to  the  demands  placed  upon  them  by  the  conditions  of 
this  experiment. 

The  excess  of  fibers  in  the  dorsal  roots  four  months  after  the 
operation,  as  compared  with  those  at  the  two-month  period, 
amounts  to  less  than  1  per  cent.  This  is  less  than  would  be  ex- 
pected on  the  basis  of  normal  growth  processes,  and  it  is  certain 
that  during  the  second  two  of  the  four  months  intervening  between 
the  operation  and  the  autopsy  there  was  no  tendency  for  the  small 
latent  cells  to  increase  their  normal  rate  of  development  in  an 
attempt  to  restore  the  atrophied  dorsal  roots  to  their  normal  con- 
dition. 

The  fact  that  both  the  ventral  and  dorsal  roots  show  more  fibers 
four  months  after  the  operation  than  at  an  earlier  period,  indicates 
very  clearly  that  there  can  be  no  slow  progressive  degeneration 
going  on  in  these  localities.  This  fact  is  of  interest,  since  retro- 
grade degeneration  has  usually  been  regarded  as  a  chronic  pro- 
gressive process.  In  this  case  it  ran  a  rather  rapid  course  and 
came  to  a  definite  termination. 

III.      Significance  of  Differences  in  the  Ages  of  the  Animals. 

It  has  been  shown  what  the  effects  of  cutting  the  second  cer- 
vical nerve  are  in  the  young  rat  and  what  influence  is  exerted  by 
the  lapse  of  a  greater  or  less  length  of  time  between  the  operation 
and  the  autopsy.  It  is  now  our  purpose  to  inquire  how  far  these 
results  are  dependent  upon  the  immaturity  of  the  animal  used  for 


^4 


Journal  of  Comparative  A  eurology  an  J  Psychology. 


the  experiment.  It  was  anticipated  that  the  section  of  the  nerve 
would  not  be  nearlv  as  destructive  of  spinal  ganglion  cells  in  the 
adult,  as  it  had  been  in  the  vounger  animals;  and  the  results  ex- 
pressed in  Table  X  came  as  something  of  a  surprise  to  the  writer. 

table  x. 

Showing    the   Effect  of  Cutting  the  II  C.  Nerve   in   Adult  Rats  (140  Days  Old) 

which  Survived  120  Days. 


Spinal  Ganglion 
Cells. 


Ventral  Root 
Fibers. 


Dorsal  Root 
Fibers. 


4,215 

610 

1,983 

4.1-b 

506 

2,219 

630 

2,176 

Average 


4-»95 


582 


2,126 


TABLE  XI. 

Showing  the  Influence  of  the  Age  of  the  Animal   and   the  Length   of  the  Post- 
operative Period  upon  the  Effect  of  Cutting  the  II  C.  Nerve  in  the  White  Rat.1 


Age  at  the  operation 

12  days 

12  days 

4  months 

Period  of  survival 

2  months 

4  months 

4  months 

Spinal  ganglion  cells    .... 

(s)  4.039 

(2)  4,268 

0)  4.195 

(4)     499 

(3)     574 

(3)     582 

(4)  1.866 

(3)  i»933 

(3)  2,126 

'The  figures  in  parentheses  indicate  the  number  of  cases  from  which  the  averages  were  obtained. 

1-  rom  1  ables  X  and  XI  it  will  be  apparent  that  there  was  found 
a  sli^hrlv  suvater  number  of  cells  in  the  spinal  ganglia  of  the  ani- 
mals operated  on  when  already  adult,  than  in  the  first  set  of  young 
rats,  bur  fewer  than  in  the  second  set.  It  is  believed  that  the 
differ  in  each  case  merely  a  matter  of  individual  variation 

in  the  original  ganglia,  and  is,  therefore,  of  no  consequence.     That 
the  section  of  the  nerve  should  entail  practically  the  same  effect 
upon  the  spinal  ganglion,  whether  it  is  made  in  the  young  or  in 
the  adult  animal,  is  a  matter  of  a  good  deal  of  interest  and  a  result 
quite  contrary  to  precedent.     It  is  the  more  difficult  to  understand 
•    JO  per  cent,  more  medulla trd  afferent  fibers  were 
CUt  in  the  operation  upon  the  adult  than  in  that  upon  the  young 
and  it  is   hard  to  sec   how   this  should    have   been  so 
ated  for  by  a  gr<  at<  r  resistance  o\  the  adult  neu- 
I  In  it    is  a  possibility  thatevenin  the  rat  twelve  days  old 


Ranson,  Degeneration  in  Spinal  Nerves. 


25 


all  the  peripheral  fibers  ever  to  develop  are  present  in  the  nerve, 
some  as  medullated,  the  rest  as  non-medullated  fibers;  and  this 
if  it  should  be  found  to  be  the  case,  would  help  to  explain  the  fact 
that  the  reaction  is  the  same  in  the  adult  as  in  the  young  animals. 
Table  XI  gives  only  the  average  number  of  cells  present  in  the 
ganglia  under  each  of  the  three  conditions;  Table  XII  shows  that 
the  agreement  which  was  found  between  the  averages  is  just  as 
apparent  when  all  the  individual  ganglia  are  brought  together. 
It  does  not  matter  whether  the  animal  is  young  or  old  or  whether 
it  survives  for  two  or  for  four  months;  the  changes  in  the  spinal 
ganglion  are  always  the  same. 

TABLE  XII. 

Showing  the  Uniformity  in  the  Cell  Destruction  in  the  Spinal  Ganglion  Resulting 
from  the  Section  of  the  Peripheral  Nerve. 


Operated  When 

Operated   When 

Operated  When 

Normal. 

12  Days  Old, 

12  Days  Old, 

140  Days  Old, 

Lived    2  Months. 

Lived  4  Months. 

Lived  4  Months. 

— 

3.845 

— 

— 

8,116 

3,896 

— 

— 

7>72i 

3.764 

— 

— 

8,624 

4,193 

4,020 

4,215 

9.343 

4,497 

4,516 

4,176 

By  reference  to  Table  XI  it  will  be  seen  that  the  number  of  ven- 
tral root  fibers  is  nearly  the  same  in  both  sets  of  rats  that  survived 
four  months,  whether  the  operation  was  made  when  they  were 
12  or  120  days  old.  This  indicates  that  the  same  number  of  ven- 
tral root  fibers  dropped  out  in  each  case,  after  which  the  nerve 
fibers  continued  to  develop  at  the  normal  rate  in  the  immature 
animal.  Hence,  since  the  number  of  medullated  fibers  was 
smaller  in  the  young  rat,  those  that  degenerated  must  have  con- 
stituted a  larger  proportion  of  the  entire  number  than  in  the  case 
of  the  adult  rat.  And  this  is  in  accord  with  the  general  belief  that 
immature  neurones  succumb  more  readily  to  an  axonal  lesion  than 
do  the  fully  developed  ones.  This  variation  in  reaction,  according 
to  the  age  of  the  animal,  is  very  pronounced  in  the  case  of  the  fibers 
of  the  corpus  callosum  (Ranson  '04).  In  a  rat  twelve  hours  old 
in  which  the  corpus  callosum  was  injured,  the  injured  fibers  under- 
went complete  degeneration,  both  Wallerian  and  retrograde; 
in  a  rat  of  three  months  the  retrograde  degeneration  affected  only 
the  part  of  the  fiber  in  the  immediate  vicinity  of  the  lesion. 


26         Journal  of  Comparative  Neurology  and  Psychology. 

The  dorsal  roots  show  distinctlv  more  fibers  in  the  animals 
operated  on  at  four  months  of  age  than  in  either  of  the  other  cases 
(Table  XI);  since,  as  Table  IV  clearly  indicates,  these  older  ani- 
mals do  not  possess  as  much  regenerative  capacity,  and  since  it 
is  certain  that  at  least  one-third  more  medullated  fibers  were  cut 
in  operating  upon  them,  it  seems  altogether  probable  that  the 
large  number  of  fibers  in  the  dorsal  roots  in  the  adult  rats  is  to  be 
explained  as  in  the  case  of  the  ventral  roots  on  the  basis  of  a  greater 
resistance  of  the  adult  neurones.1 

The  interpretation  of  the  numerical  results  obtained  for  the 
spinal  ganglion  and  dorsal  root  is  exceedingly  difficult.  A  final 
statement  can  only  be  made  when  we  have  the  results  of  the 
Marchi  test  and  the  Nissl  stain  to  assist  us  in  drawing  conclu- 
sions, since  in  these  ways  we  can  tell  what  proportion  of  the  fibers 
degenerate  and  whether  the  large  or  the  small  cells  are  chiefly 
concerned  in  the  changes  going  on  in  the  ganglion.  Investigations 
along  these  lines  are  now  in  progress. 

1  At  first  sight  it  seems  a  contradiction  to  sav  that  the  dorsal  roots  show  varying  degrees  of  resistance 
but  that  there  is  no  difference  in  the  degree  of  degeneration  seen  in  the  spinal  ganglion.  If,  however, 
it  were  the  small  cells  not  directly  associated  with  medullated  fibers  that  had  disappeared  from  the 
ganglion  it  would  be  easy  to  understand  how  the  dorsal  root  fibers,  associated  as  they  are  with  the  large 
cells,  would  be  quite  independent  of  the  decrease  in  the  number  of  the  ganglion  cells.  These  large  cells 
with  their  medullated  processes  would  then  suffer  varying  degrees  of  injury,  usually  not  resulting  in 
the  destruction  of  the  perikarya,  but  in  a  certain  proportion  of  the  cases  bringing  about  a  degeneration 
of  the  associated  dorsal  root  fibers.  The  more  mature  the  animal,  the  less  seriously  would  the  large 
neurones  be  injured,  and  the  fewer  would  those  be  that  could  not  maintain  their  dorsal  root  fibers  intact. 

The  possible  causes  of  variation  in  the  dorsal  roots  may  be  stated  as  follows: 

i.  While  the  total  number  of  cells  destroyed  is  constant,  the  proportion  of  large  and  small  cells 
affected  may  vary,  and  accompanying  a  greater  destruction  of  large  cells,  there  may  be  a  greater 
degeneration  of  the  dorsal  root.     This  supposition  is  very  improbable. 

2.  All  the  large  cells  may  drop  out  in  every  case,  the  variation  in  the  dorsal  roots  depending  upon 
the  extent  of  the  compensatory  development  of  the  small  cells. 

\.  Most  of  the  large  cells  may  pass  through  the  stages  of  reaction  and  repair,  while  the  small  cells 
drop  out  in  large  numbers.  In  this  case  the  medullated  nerve  fibers  a  sociated  with  a  varying  number 
of  large  neurones  might  degenerate  although  the  perikarya  of  these  same  neurones  survive.  This  is 
the  most  probable  explanation  of  the  results,  as  will  be  shown  in  another  paper.  At  the  present  moment 
■ins  probable  that  the  key  to  the  explanation  of  all  these  conflicting  results  is  to  be  found  in  the 
of  many  non-medullated  fibers  which  are  the  axons  of  the  small  cells.  This  would 
furnish  an  explanation  f'>r  the  degeneration  of  the  i  mall  eel  In  after  th<      i  tion  ol  i  lie  nerve. 


Ranson,  Degeneration  in  Spinal  Nerves.  2J 

IV.     Effect  of  Reunion  of  the  Cut  Ends  of  the  Divided  Nerves. 

It  is  clear  from  Table  IV  that,  so  far  as  the  survival  of  spinal  gan- 
glion cells  is  concerned,  it  is  a  matter  of  indifference  whether 
regeneration  of  the  nerve  occurs  or  not.  In  four  cases  no  regenera- 
tion occurred  at  all;  in  the  other  six  cases  the  extent  of  the  regenera- 
tion varied  considerably;  in  one  case  (14)  an  almost  perfect  nerve 
was  found,  with  only  a  slight  thickening  to  indicate  the  point  of 
division.  But  with  this  wide  range  in  the  degree  of  the  restoration 
of  the  peripheral  nerve,  there  is  no  difference  in  the  condition  of 
the  spinal  ganglion.  This  shows  very  clearly  that  the  degenera- 
tion of  spinal  ganglion  cells  is  not  markedly  influenced  by  the 
regeneration  or  lack  of  regeneration  of  the  peripheral  nerve. 
Marinesco  ('98)  states  that  unless  there  is  union  of  the  divided 
ends  of  the  nerve,  the  motor  cells  of  the  ventral  cornua  do  not 
pass  from  the  phase  of  reaction  to  the  phase  of  restoration,  but 
atrophy  and  disappear.  The  entrance  upon  the  phase  of  restora- 
tion is,  according  to  him,  an  indication  that  regeneration  has  begun 
in  the  nerve.  Van  Gehuchten  ('99)  and  Foa  ('99)  have  been 
unable  to  confirm  these  observations  of  Marinesco  for  the  motor 
nuclei,  and  my  results  would  indicate  that  for  the  spinal  ganglia 
the  restoration  of  the  cells  is  entirely  independent  of  the  restoration 
of  the  peripheral  nerve. 

CONCLUSIONS. 

As  a  result  of  dividing  a  peripheral  nerve,  there  occurs  not  only 
the  typical  Wallerian  degeneration  of  the  distal  portion  but  also 
various  changes  in  the  proximal  portion  of  the  nerve,  the  spinal 
ganglion,  the  ventral  and  dorsal  roots  and  the  spinal  cord.  In 
all  these  regions  there  take  place  both  a  simple  atrophy  and  a  true 
degeneration.  The  atrophy  results  in  a  decrease  in  the  size  of 
the  fibers,  many  of  which  entirely  lose  their  medullary  sheaths. 
Many  of  the  cellsof  the  ventral  cornua  and  of  the  spinal  ganglion 
are  markedly  atrophic.  The  degeneration  in  the  fibers  proximal 
to  the  lesion  begins  some  weeks  later  than  Wallerian  degeneration, 
from  which,  however,  it  cannot  be  distinguished  histologically.  This 
retrograde  degeneration  affects  only  a  part  of  the  fibers  and  can 
be  found  not  only  in  the  central  stump  and  the  ventral  and  dorsal 
roots  but  also  in  the  intramedullary  continuations  of  the  root  fibers. 
This  results  in  a  distinct  diminution  of  the  number  of  nerve  fibers 


28  Journal  of  Comparative  Neurology  an  J  Psychology. 

in  these  regions  and  helps  to  increase  their  atrophic  appearance. 
The  degeneration  of  nerve  cells  results  in  the  disappearance  of  a 
certain,  apparently  variable,  number  of  ventral  horn  cells  and  a 
very  considerable  and  constant  number  of  spinal  ganglion  cells. 

It  has  been  shown  by  careful  enumeration  that  after  cutting 
the  second  cervical  nerve  of  the  white  rat,  one-half  of  the  cells  in 
the  corresponding  spinal  ganglion  degenerate  and  disappear. 
This  reaction  is  very  constant  and  uniform;  in  the  nine  ganglia 
studied  the  percentage  of  variation  is  no  greater  than  the  percent- 
age of  individual  variation  in  the  normal  ganglia.  This  is  pe- 
culiar in  that  many  more  cells  disappear  than  can  be  accounted 
for  in  terms  of  medullated  fibers  cut  at  the  time  of  the  operation; 
and  while  it  is  not  possible  at  present  to  give  a  satisfactory  ex- 
planation of  the  results  they  point  to  some  as  yet  unknown 
relations  in  the  ganglion. 

The  number  of  fibers  in  the  dorsal  root  is  open  to  much  greater 
variation;  but  there  is  on  the  average  a  loss  of  about  17  per  cent. 
The  dorsal  roots  seem  more  susceptible  to  the  degenerative 
changes  in  the  young  than  in  adult  animals. 

to  J    _        o 

The  degeneration  of  ganglion  cells  is  constant,  that  of  the  dorsal 
root  fibers  is  variable  and  is  much  less  extensive  than  would  be 
expected  from  the  number  of  cells  which  disappear.  This  shows 
that  the  degeneration  in  the  dorsal  roots  cannot  without  some 
qualification  be  attributed  to  the  degeneration  in  the  spinal  gan- 
glion. It  is  hoped  that  an  investigation  now  in  progress  will  sup- 
ply the  necessary  data  for  the  interpretation  of  these  results. 

Contrary  to  the  usual  conception,  the  degeneration  of  fibers  and 
cells  was  not  progressive;  it  had  been  completed  before  the  end 
of  the  first  two  months,  after  which  there  was  no  further  change. 

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